Our long-term objective is to design and prepare chemicals that contribute to the development of molecular probes or pharmaceuticals with anti infective properties. Because of their relationship to potential antimetabolites of natural carbohydrates, antiulcer agents, prostacyclin (PGI2) analogues, polyether antibiotics and potential human immunodeficiency virus (HIV) reverse transcriptase inhibitors, and many other important synthetic and natural products, methodologies for the synthesis of enantiomerically pure substituted tetrahydrofuran- and pyrrolidine derivatives are the focus of extensive research. Recently, we developed an experimentally straightforward method for the regio- and stereoselective formation of tetrahydrofuranylidenes and spiroketals via thermal cyclization of dihydroxyketone equivalents and synthesized regio- and stereoselectively four tri- and terasubstituted E-1-(benzenesulfonyl)-1-tetrahydrofuranylidenes from their corresponding alpha'-benzenesulfonyl-gamma-hydroxyketones in good yields. Examination of the regio- and stereoselectivity of these thermally induced reactions showed preference for both, the exocyclic nature of the double bond and the E - geometry in all tetrahydrofuranylidenes synthesized. This research is a chemically and pharmacologically useful extension of our methodology. Specifically, the emphasis of this project is to apply stereocontrolled cyclization methodology of amino- and hydroxy- ketosulfone derivatives to accomplish the synthesis of: 1. Chiral Tetrahydrofuranylidenes, 2. Chiral Tetrahydrofuran Derivatives and Aza Analogues, 3. Target Pharmacologically Active Compounds, and 4. Substructures of Potentially Therapeutic Agents isolated from higher plants. The combined data and chemical compounds obtained from this research will add to the understanding of the chemical reactivity of non aromatic medium-ring oxygen and nitrogen heterocytes for its use in stereochemically improved drug design, to increase their potency, safety and effectiveness. Also, this project will provide interested and talented minority undergraduate students with opportunities to develop basic research skills, and will prepare and motivate them to continue graduate studies in the biomedical sciences, through the following proposed activities: 1.. research along side faculty members, 2. Off-Campus Student Summer Research Enrichment Experience, 3. active participation in local and National meetings in areas of biomedical research, and 4. active participation in group meetings, special seminars in the areas of chemistry, biochemistry, biology and biotechnology.